Intermediates for the production of vitamin b6 and processes of preparing the same



Patented July 19, 1949 UNITED STATES v TENT OFFICE IN TERMEDIATES FORTHE PRODUCTION OF VITAMIN B6 AND PROCESSES OF PREPAR- ING THE SAME EricT. Stiller, Chagrin Falls, Ohio, assignr to Merck & 00., Inc., Rahway,N. J a corporation of New Jersey N0 Drawing. Original applicationNovember 15,

1940, Serial No. 365,758. Divided and this application January 4, 1945,Serial No. 571,361

6 Claims.

R1 ON CH3 N O H wherein R is selected from the group consisting ofmethyl and alkoxymethyl, and R1 is selected from the group consisting ofacylamino, acylam'inomethyl and aminomethyl, are valuable intermediatesfor the production of vitamin B6.

The novel compounds of the present invention may be prepared, forexample, by reacting 3- cetylamino-acetyl-acetone with cyanoacetamide inthe presence of an organic solvent, and a basic catalyst selected fromthe group consisting of an aliphatic amine and a saturated heterocyclicamine to form 3-cyano-4,6-dimethyl-5-acetylaminc-pyridone-Z.

Upon reacting S-acetylamino-l-ethoxypentane- 2,4-dione andcyanoacetamide in the presence of an organic solvent, and the abovebasic catalyst, there is obtained 3-cyano-4-ethoxymethyl-5-acetylamino-6-methyl-pyridone-2.

Upon reacting 3benzoylaminomethyl-pentane- 2,4-dione with cyanoacetamidein the presence of an organic solvent, and the above basic catalyst,there is obtained 3-cyano-4,6-dimethyl benzoylaminomethyl-pyridone-2.

Upon reacting 1-ethoxy-S-benzoylaminomethyl-pentane-2,4-dione andcyanoacetamide in the presence of an organic solvent, and the abovebasic catalyst, there is obtained 3-cyano-4- ethoxymethyl- 5-benzoy1aminomethyl-G-methylpyridone-Z.

Example I 0.5 gm. of 3-acety1amino-acetyl-acetone are mixed with 0.27gm. of cyanoacetamide, and dissolved in 18 cc. of alcohol. Three dropsof piperidine are added, and the solution refluxed for 45 minutes,during which time crystalline material separates. On cooling, thecrystalline material is filtered off, and recrystallized from alcohol.3-cyano 4,6 dimethyl-5-acetylamino pyridone-z is obtained as colorlessneedles, M. P. above 300 C. Yield 0.3 gm.

Example II 2 gins. of 3-acetylamino-1-ethoxypentane-2,4- dione and 0.85gm. of cyanoacetamide are dissolved in 25 cc. of alcohol, and six dropsof piperidine are added. The mixture is refluxed for two hours and thencooled to 0 C. After standing for some hours, the crystalline materialis filtered ofi, and recrystallized from alcohol.3-cyano-4-ethoxymethyl-5-acetylamino-G-meth yl-pyridone-Z is obtained asclusters of colorless fine'needles, M. P. 262-3 (decomposition).

Example III 0.55 gm. of 3-benzoylaminomethyl-pentane- 2,4 dione in 10cc. of dioxane are mixed with 0.2 gm. of cyanoacetamide, and two dropsof piperidine are added. The mixture is refluxed for three hours. Oncooling, and the addition of a little water, crystallization takesplace. 3-cyano- 4,6-dimethyl-5-benzoylaminomethyl pyridone-2 is obtainedin the form of colorless prisms, M. P. 316 C. (decomposition).

Earample IV 1.65 gms. of 1-ethoxy-3-benzoylaminomethylpentane-2,4-dioneare dissolved in 20 cc. of ethyl alcohol and 0.5 gm. cyanoacetamide, 2drops of piperldine are added, and the mixture boiled under reflux forthree hours. On cooling, 0.37 gm. of3-cyano-4-ethoxymethyl-B-benzoylaminomethyl 6-methyl-pyridone-2 areobtained as pale yellow plates. The product is purified by dissolving inglacial acetic acid, followed by the addition of a small amount ofwater, and is obtained as small colorless plates, M. P. 275-6 C.(decomposition).

If desired, the end products of Examples 1 and 2 may be hydrolyzed tothe 5-amino compound by treatment with hydrochloric acid, and the endproducts of Examples 3 and 4 may be hydrolyzed to the 5-aminomethylcompound by treatment with hydrochloric acid.

Other alkoxymethyl substituents in the 4 position may be obtained, forexample, by condensing 1-methoxy-3-acetylamino-pentane-2,4-dione, or1-methoxy 3 benzoylaminomethyl-pentane 2,4-dione with cyanoacetamide inthe presence of an organic solvent and the basic catalyst.

Other pyridones, having an acylamino or acylamino-methyl group as asubstituent in the 5 position, may be obtained by condensing otherappropriate 1 alkoxy 3 acylamino-pentane-2,4- diones 01l-alkoxy-B-acylaminomethyl-pentane- 2-4-diones with cyanoacetamide inthe presence of an organic solvent and the basic catalyst. Pyridones ofthis type are disclosed in my copend-1-alkoxy-3-acylaminomethyl-pentane-2:4 dione and cyanoacetamide in thepresence of an organic solvent, and a basic catalyst selected from thegroup consisting of an aliphatic amine and a saturated heterocyclicamine and recovering 3- cyano 4 alkaoxymethyl-5-acylaminomethy1-6methyl-pyridone-2.

4. S-cyano 4 methoXymethVI-BFacetylaminomethyl-6-methyl-pyridone-2.

5. In the process for preparing a vitamin 36 intermediate, the stepswhich comprise reacting l-ethoxy 3 benzoylaminomethyl pentane-2,4- dioneand cyanoacetamide in the presenc f n organic solvent, and a basiccatalyst selected from the group consisting of an aliphatic amine and asaturated heterocyclic amine and recovering 3 cyano 4ethoxymethyl-5-benzoylaminomethyl-.6-methyl-pyridone-2.

6. In the process of preparing a vitamin B6 intermediate, the stepswhich comprise reacting 'l-methoxy g 3 acetylaminomethyl pentane-2,4-

dione and .cyanoacetamide in the presence of an or anic solvent, and. abasic catalyst selected from the group consisting of an aliphatic amineand a saturated heterocyclic amine and recovering 3 cyano 4methoxymethyl-S-acetylaminomethyl-6-methyl-pyridone-2.

ERIC T. STILLER.

No references cited.

